赤芍总苷通过Nrf2/HO-1通路对糖尿病肾脏病大鼠肾纤维化的改善作用研究  

The Effect of Total Paeony Glycosides on Renal Fibrosis in Diabetic Kidney Disease Rats Through Nrf2/HO-1 Pathway

作　　者：王鑫 申亮 王培珍 WANG Xin;SHEN Liang;WANG Peizhen(Hengshui Hospital of Traditional Chinese Medicine,Hengshui Hebei 053000,China;Fengfeng General Hospital,North China Medical Group,Handan Hebei 056200,China;Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine,Cangzhou Hebei 061000,ChAina)

机构地区：[1]衡水市中医医院,河北衡水053000 [2]华北医疗集团峰峰总医院,河北邯郸056200 [3]河北省沧州中西医结合医院,河北沧州061000

出　　处：《中医药导报》2023年第4期5-10,16,共7页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：河北省中医药管理局2022年中医药类科研计划项目(2022670)。

摘　　要：目的:探讨赤芍总苷(TPG)对糖尿病肾脏病(DKD)大鼠肾纤维化的改善效果及可能作用机制。方法:从60只雄性Wistar大鼠中随机选择10只作为对照组,剩余50只大鼠利用尾静脉注射链脲佐菌素(55 mg/kg)诱导DKD大鼠模型。成功建模43只,随机选择40只并随机分为模型组、TPG低剂量组、TPG高剂量组及二甲双胍组,每组10只。各给药组分别灌胃给予相应药物,模型组和对照组灌胃给予等体积生理盐水,连续给药12周观察大鼠一般状态,计算肾脏指数(KI);采用ELISA法测量24 h尿白蛋白(Alb)含量;采用生化分析仪检测各组大鼠空腹血糖(FBG)、血肌酐(Scr)、血尿素氮(BUN)水平;HE染色观察肾脏组织形态学变化;高碘酸-希夫(PAS)染色观察系膜基质、基底膜组织学变化;Masson染色观察胶原蛋白沉积情况;采用比色分析法检测大鼠肾组织中氧化应激因子丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性;采用Western blotting法检测总转录因子NF-E2相关因子2(Nrf2)、核Nrf2、血红素加氧酶1(HO-1)、平滑肌肌动蛋白(α-SMA)、纤连蛋白(FN)的相对表达量。结果:成功构建DKD大鼠模型;模型组大鼠一般体征失常,肾组织出现明显病理变化,肾组织结构改变,炎症细胞浸润明显,肾小球系膜基质扩张、基底膜增厚,胶原蛋白过度沉积,肾纤维化严重。TPG低、高剂量组及二甲双胍组大鼠一般体征逐渐恢复正常,病理损伤逐渐好转,肾小球系膜基质范围减小、基底膜变薄,胶原蛋白沉积减弱,肾纤维化逐渐改善。模型组大鼠KI,24 h尿Alb含量,FBG、Scr、BUN,以及肾组织中MDA含量和α-SMA、FN蛋白相对表达量均高于对照组(P<0.05);肾组织中SOD活性、核Nrf2、HO-1蛋白相对表达量均低于对照组(P<0.05)。TPG低、高剂量组及二甲双胍组大鼠KI,24 h尿Alb含量,FBG、Scr、BUN,以及肾组织中MDA含量和α-SMA、FN蛋白相对表达量均低于模型组(P<0.05);肾组织中SOD活性、核Nrf2、HO-1Objective:To investigate the effect and possible mechanism of total paeony glycoside(TPG)on renal fibrosis in diabetic kidney disease(DKD)rats.Methods:Ten of 60 male Wistar rats were randomly selected as the control group,and the remaining 50 rats were injected with streptozotocin(55 mg/kg)into the tail vein to induce DKD rat model.43 rats were successfully modeled,and 40 rats were randomly selected and randomly divided into model group,TPG low-dose group,TPG high-dose group and metformin group,with 10 rats in each group.Each administration group was given corresponding drugs by gavage,and the model group and the control group were given equal volume of normal saline by gavage for 12 weeks.The general state of rats was observed and the kidney index(KI)was calculated.The content of 24 h urinary albumin(Alb)was measured by ELISA.The levels of fasting blood glucose(FBG),serum creatinine(Scr)and blood urea nitrogen(BUN)were detected by biochemical analyzer.HE staining was used to observe the morphological changes of kidney tissue.The histological changes of mesangial matrix and basement membrane were observed by periodic acid-Schiff(PAS)staining.Collagen deposition was observed by Masson staining.The content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in renal tissue were detected by colorimetric analysis.The relative expression levels of total transcription factor NF-E2 related factor 2(Nrf2),nuclear Nrf2,heme oxygenase 1(HO-1),smooth muscle actin(α-SMA)and fibronectin(FN)were detected by Western blotting.Results:The DKD rat model was successfully constructed.The rats in the model group had abnormal general signs,obvious pathological changes in renal tissue,changes in renal tissue structure,obvious infiltration of inflammatory cells,expansion of glomerular mesangial matrix,thickening of basement membrane,excessive deposition of collagen,and severe renal fibrosis.The general signs of rats in the TPG low-dose group,TPG high-dose group and metformin group gradually returned to normal,the pathol

关 键 词：糖尿病肾脏病 肾纤维化 赤芍总苷 转录因子NF-E2相关因子2 血红素加氧酶1 大鼠 

分 类 号：R285.5[医药卫生—中药学]